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Bisphosphonates are effective treatment for osteoporosis, but upper gastrointestinal injury associated with some compounds has caused concern. This study compared the incidence of gastric ulcers after treatment with risedronate, a pyridinyl bisphosphonate, and alendronate, a primary amino bisphosphonate. Esophageal and gastroduodenal injury assessed by endoscopy scores was a secondary endpoint.Healthy, postmenopausal women (n = 515) received 5 mg risedronate (n = 255) or 10 mg alendronate (n = 260) for 2 weeks. At baseline and on days 8 and 15, subjects underwent endoscopy and evaluator-blinded assessment of the esophageal, gastric, and duodenal mucosa.Gastric ulcers were observed during the treatment period in 9 of 221 (4.1%) evaluable subjects in the risedronate group compared with 30 of 227 (13.2%) in the alendronate group (P0.001). Mean gastric endoscopy scores for the risedronate group were lower than those for the alendronate group at days 8 and 15 (P/= 0.001). Mean esophageal and duodenal endoscopy scores were similar in the 2 groups at days 8 and 15. Esophageal ulcers were noted in 3 evaluable subjects in the alendronate group, compared with none in the risedronate group, and duodenal ulcers were noted in 1 evaluable subject in the alendronate group and 2 in the risedronate group.At doses used for the treatment of osteoporosis, risedronate was associated with a significantly lower incidence of gastric ulcers than alendronate. These findings confirm that bisphosphonates differ in their potential to damage the gastroesophageal mucosa.

Ninety normal volunteers were entered into a double-blind, placebo-controlled study to compare the efficacy of misoprostol (200 micrograms q.i.d.) vs. cimetidine (300 mg q.i.d.) in protecting the gastric and duodenal mucosa from tolmetin-induced (400 mg q.i.d.) injury. After 6 days of treatment, the degree of mucosal injury between treatments was compared by endoscopy, using a predetermined rating scale of 0 (normal mucosa) to 4+ (greater than 25 hemorrhages or erosions or an invasive ulcer). Utilizing a score of less than or equal to 2+ (2-10 hemorrhages or erosions) as a therapeutic success, the overall success rates were 8/30 (26.7%) for placebo, 19/30 (63.3%) for cimetidine, and 27/29 (93.1%) for misoprostol (p less than 0.001). Pairwise comparisons were also significant: misoprostol vs. placebo (p less than 0.001), misoprostol vs. cimetidine (p = 0.006), and cimetidine vs. placebo (p = 0.004). A separate analysis of the gastric scores alone revealed success rates identical to those in the overall evaluation; however, success rates in the duodenum for both misoprostol (29/29) and cimetidine (29/30) were extremely high and did not differ. It is concluded that misoprostol is highly effective and significantly better than cimetidine in protecting the gastric mucosa from tolmetin-induced injury; however, both agents were highly protective in the duodenum.

Although bougienage is widely used to treat benign esophageal stricture, the rate of stricture recurrence and the long-term effectiveness of bougienage are unknown. We studied the natural history of esophageal stricture in 154 patients in whom bougienage was used as primary therapy. Dilatations were considered successful in terms of relief or major improvement of dysphagia in 84.5% of 103 patients followed 6 mo or longer (median, 26 mo). The risk of requiring esophageal dilatation after the initial episode was greatest in the first year of follow-up; thereafter, a smaller fraction of patients required dilatation each year. Forty-three percent of patients required no further dilatations, and a life-table analysis showed that 36% of patients would require no further dilatation during a projected 4-yr follow-up. The median frequency of subsequent dilatation was less than once a year. We were unable to identify any significant factors, such as initial severity of stricture, cause of stricture, presence of active esophagitis, or initial caliber of dilatation, that could predict the need for subsequent dilatation. Our results suggest that patients with benign strictures fall into two groups. In one group, the natural history was to improve or become asymptomatic after an initial series of dilatations, and only a small proportion eventually developed recurrent symptoms. The second group (46% of patients) required further dilatations to treat dysphagia during the first year of follow-up. Two-thirds of these patients needed regular dilatations in subsequent years. We conclude that bougienage is effective treatment for benign esophageal strictures, and should be utilized as primary therapy for most strictures.

A 54-year-old man presenting with fever, hepatomegaly, and weight loss was found to have acute histoplasmosis, apparently involving only the liver. The diagnosis was established by culture of liver biopsy material and elevated complement fixation titers which declined in the convalescent phase of the patient's illness. Histological examination showed only granulomatous hepatitis. The patient recovered uneventfully without the use of systemic antifungal drugs. He did receive corticosteroids for a brief period. The patient now has been followed for 3 years and remains well. A recent liver biopsy showed only minimal periportal lymphocytic infiltration. A review of the literature fails to reveal a similar case. An analogy is drawn between this case and the acute self-limited pulmonary form of histoplasmosis. Culture of liver biopsy material showing granulomatous hepatitis is recommended in all cases where the etiology is not clear from other evidence.

Although bougienage is widely used to treat benign esophageal stricture, the rate of stricture recurrence and the long-term effectiveness of bougienage are unknown. We studied the natural history of esophageal stricture in 154 patients in whom bougienage was used as primary therapy. Dilatations were considered successful in terms of relief or major improvement of dysphagia in 84.5% of 103 patients followed 6 mo or longer (median, 26 mo). The risk of requiring esophageal dilatation after the initial episode was greatest in the first year of follow-up; thereafter, a smaller fraction of patients required dilatation each year. Forty-three percent of patients required no further dilatations, and a life-table analysis showed that 36% of patients would require no further dilatation during a projected 4-yr follow-up. The median frequency of subsequent dilatation was less than once a year. We were unable to identify any significant factors, such as initial severity of stricture, cause of stricture, presence of active esophagitis, or initial caliber of dilatation, that could predict the need for subsequent dilatation. Our results suggest that patients with benign strictures fall into two groups. In one group, the natural history was to improve or become asymptomatic after an initial series of dilatations, and only a small proportion eventually developed recurrent symptoms. The second group (46% of patients) required further dilatations to treat dysphagia during the first year of follow-up. Two-thirds of these patients needed regular dilatations in subsequent years. We conclude that bougienage is effective treatment for benign esophageal strictures, and should be utilized as primary therapy for most strictures.

Although nocturnal acid secretion has been emphasized in the pathophysiology and treatment of duodenal ulcer, its importance in gastric ulcer disease has been questioned. To explore this area, this multicenter U.S. trial compared the effect of a once-daily nighttime dose of H2-receptor antagonist with placebo on the healing of gastric ulcer and relief of associated symptoms. One hundred fifty-seven patients with endoscopically verified benign gastric ulcers were randomized in a double-blind fashion to either famotidine (40 mg at bedtime) or placebo. Antacid tablets were allowed as needed. The healing rates for famotidine were 45%, 66%, and 78% at weeks 4, 6, and 8, respectively. In comparison, placebo healing rates were 39%, 44%, and 64%. These differences were statistically significant in favor of famotidine at weeks 6 (p less than or equal to 0.01) and 8 (p less than or equal to 0.05), as well as in a life-table analysis (p less than or equal to 0.05). Nocturnal famotidine was also significantly better than placebo with respect to time to complete relief of pain and to the percentage of patients with complete relief of pain. No concomitant factor (including ulcer size, ulcer location, smoking history, or regular alcohol use) affected healing rates in this study. Famotidine was well-tolerated and no serious clinical or laboratory adverse effects were judged to be related to this dosing regimen of famotidine. In conclusion, suppression of nocturnal acid secretion with famotidine (40 mg at bedtime) was more effective than placebo in promoting the healing of acute benign gastric ulcer and its associated symptoms. The results of this study suggest that suppression of nocturnal acid secretion alone is as effective as "around the clock" acid suppression in the healing of benign gastric ulcer.